To study the inhibitory effect of Fuzheng Yiliu Granule (ae parts per thousand ae aeSc pound similar to currency signe cent uc(2)', FYG) on hepatocellular cancer (HCC) and investigate the mechanism mediating its bioactivity. H22 tumor-bearing ICR mice were treated with FYG [3.6 g/(kg center dot d)] for 5 days. Tumor volume and tumor weight, percentages of CD3(+), CD4(+), CD8(+), and natural killer (NK) cells in peripheral blood, tumor apoptosis and serum levels of interleukin-2 (IL-2), and tumor necrosis factor-alpha (TNF-alpha) were evaluated. FYG-containing serum was prepared from SD rats treated for 7 days [high dose 3.6 g/(kg center dot d); middle dose 1.8 g/(kg center dot d); low dose 0.9 g/(kg center dot d)]. Cell cycle, cell viability, and apoptosis were evaluated after HepG2 cell line was cultured in FYG-containing serum for 48 h. The levels of IL-2 and TNF-alpha in FYG-containing serum were also determined. FYG produced a potent antitumor effect (P < 0.01) and induced marked apoptosis of the tumor tissue (P < 0.05). Mice treated with FYG had higher percentages of CD3(+) and CD4(+) (P < 0.05), and more NK cells (P < 0.01) in the peripheral blood than those in the animals treated with normal saline. Mice receiving FYG had the highest serum levels of IL-2 and TNF-alpha (P < 0.01). High-dose FYG-containing serum significantly decreased HepG2 cell viability, inhibited cell proliferation (P < 0.05), and induced apoptosis (P < 0.01). In addition, the levels of IL-2 and TNF-alpha of high-dose-containing serum were higher than the blank serum (P < 0.01). FYG could inhibit HCC growth by regulating immune function and inducing apoptosis of tumor cells in vivo and in vitro.